Diastolic filling of the left ventricular is impaired in many patients with hypertrophic cardiomyopathy. Although verapamil improves indices of diastolic filling in many patients with this disease, the relation between improved diastolic filling and improved exercise tolerance has not been demonstrated. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 43 patients by radionuclide angiography and graded treadmill testing before and after 1-4 weeks of oral verapamil therapy, 320-480 mg per day. The verapamil-induced increase in peak left ventricular filling rate (PFR) at rest was associated with a increased exercise tolerance: exercise capacity increased in 28 of 32 patients manifesting an increase in PFR but only 3 of 11 patients with unchanged or decrease PFR. This initial trend persisted in 23 patients studied after 1 year of therapy: 11 of 14 patients with a persistent increase in PFR had persistent improvement in exercise tolerance relative to pre-verapamil values, compared to only 1 of 9 patients in whom PFR was unchanged or decreased relative to pre-verapamil values. Hence, verapamil-induced changes in left ventricular PFR were associated significantly with objective symptomatic improvement. These data indicate that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many hypertrophic cardiomyopathy patients during verapamil therapy.